Affinity-based drug delivery is a class of delivery systems that has recently gained popularity. These systems intentionally incorporate affinity moieties that interact with the agent of interest to control and manipulate its loading and release. Drug release rates from these systems are governed by the kinetic parameters in binding and release between the drug and the affinity moieties within the delivery systems, not by diffusion alone. As a result, release can be tailored based on the strength of these interactions. Affinity-based drug delivery systems have been used in the delivery of antibiotics, chemotherapy agents and growth factors. Wang, N. X.; von Recum, H., Macromol Biosci 11(3), 321-32 (2011); Maxwell et al., Acta Biomater 1(1), 101-13 (2005). The affinity used in drug delivery systems can be based on numerous interactions, including charge, hydrophobicity, and van der Waals forces.
Examples of affinity-based drug delivery systems include polycations, albumin, cyclodextrins, molecular imprinting, and heparin binding. Polycations are typically used for administering nucleic acids K. A. Howard, Adv. Drug Delivery Rev. 61, 710 (2009). Albumin has a high affinity for metal ions, fatty acids, amino acids, and numerous drug compounds. Fehske et al., Biochem. Pharmacol. 30, 687 (1981). Cyclodextrins are cyclic oligosaccharides that enable cyclodextrins to complex with small hydrophobic drugs and or molecules, and is typically used to increase hydrophilicity. A hydrogel including β-cyclodextrin with isocyanate crosslinking has been developed for delivering antibiotics. T. R. Thatiparti, H. A. von Recum, Macromol. Biosci. 10, 82 (2010). Molecular imprinting is a method use to form biomimetic polymer networks with template-shaped cavities that increase affinity for specific molecules of interest. Because of readily adaptable and rapid synthesis, close resemblance to molecular recognition, and availability of functional monomer libraries, use of non-covalent interactions has proven to be the most popular. S. Wei, B. Mizaikoff, J. Sep. Sci. 30, 1794 (2007). After establishing a non-covalent interaction between functional monomers and the template of choice, the monomers are polymerized with the template molecule still present, after which the template molecule is remove, leaving behind a template shaped cavity with affinity for the molecule of interest. E. Oral, N. A. Peppas, J. Biomed. Mater. Res., A 78, 205 (2006).
Heparan sulfate is a naturally occurring, highly sulfated anionic glycosaminoglycan found in the extracellular matrix that is responsible for immobilizing and releasing various proteins that influence natural processes such as cell adhesion, migration, proliferation, and differentiation. The specific heparin binding domain on numerous growth factors is highly specific and can interaction with heparin via non-covalent interactions. S. E. Sakiyama-Elbert, J. A. Hubbell, J. Controlled Release 65, 389 (2000). RANTES and its derivatives are known to have affinity interactions with various glycosaminoglycans (GAGs), with heparin having the strongest affinity, followed by various chondroitin sulfates (von Recum et al., Tissue Eng 5(3), 251-65 (1999) and uncleaved heparan sulfates. Brandner et al., Protein Eng Des Sel, 22(6), 367-73 (2009). These interactions have been explored in the application of biosensor and diagnostic development for cytokines. Duo et al., Anal Bioanal Chem, 399(2), 773-82 (2011); Duo, J.; Stenken, J. A., Anal Bioanal Chem., 399(2), 783-93 (2011).